OBJECTIVE: To assess the usefulness of case reports as sources for research on diagnostic errors in uncommon diseases and atypical presentations.
BACKGROUND: We reviewed 563 case reports of diagnostic error. The commonality of the final diagnoses was classified based on the description in the articles, Orphanet, or epidemiological data on available references; the typicality of presentation was classified based on the description in the articles and the judgment of the physician researchers. Diagnosis Error Evaluation and Research (DEER), Reliable Diagnosis Challenges (RDC), and Generic Diagnostic Pitfalls (GDP) taxonomies were used to assess the factors contributing to diagnostic errors.
UNASSIGNED: Excluding three cases in that commonality could not be classified, 560 cases were classified into four categories: typical presentations of common diseases (60, 10.7 %), atypical presentations of common diseases (35, 6.2 %), typical presentations of uncommon diseases (276, 49.3 %), and atypical presentations of uncommon diseases (189, 33.8 %). The most important DEER taxonomy was \"Failure/delay in considering the diagnosis\" among the four categories, whereas the most important RDC and GDP taxonomies varied with the categories. Case reports can be a useful data source for research on the diagnostic errors of uncommon diseases with or without atypical presentations.

We report herein the synthesis and characterization of three heterocyclic curcuminoid ligands and their homoleptic metal complexes with magnesium and copper. Thus, N-methyl-2-pyrrolecarboxaldehyde, Furan-2-carboxaldehyde, and 2-Thiophenecarboxaldehyde were condensed with 2,4-pentanedione-boron trioxide complex. The first N-methyl-2-pyrrole curcuminoid and its Mg(II) complex are reported. All curcuminoid ligands and their corresponding metal complexes were characterized by infrared spectroscopy (IR), liquid state nuclear magnetic resonance (LSNMR), electron paramagnetic resonance (EPR), mass spectrometry (MS) and single crystal X-ray diffraction (SCXRD). The ThiopheneCurc-Cu (9) constitutes the first case of a \"conformationally-heteroleptic\" complex. The unique six-peaks star arrangement for the ThiopheneCurc ligand derived from the supramolecular description is reported. The metal complexes of FuranCurc-Mg (5) and ThiopheneCurc-Cu (9) have a good antioxidant effect (IC50 = 11.26 ± 1.73 and 10.30 ± 0.59 μM), three and two times higher than their free ligands respectively. Additionally, (5) shows remarkable cytotoxicity against colon cancer adenocarcinoma cell line HCT-15, comparable to that of cisplatin, with a negligible toxic effect in vitro towards a healthy monkey kidney cell line (COS-7).

Relaxation-induced dipolar modulation enhancement (RIDME) time trace shapes reveal linear scaling with the proton concentration in homogeneous glassy samples. We describe here an approximate diffusion equation-based analysis of such data, which uses only two fit parameters and allows for global data fitting with good accuracy. By construction, the approach should be transferable to other pulse EPR experiments with longitudinal mixing block(s) present. The two fit parameters appear to be sensitive to the type of the glassy matrix and can be thus used for sample characterisation. The estimates suggest that the presented technique should be sensitive to protons at distances up to 3 nm from the electron spin at a 90% matrix deuteration level. We propose that a structural method might be developed based on such an intermolecular hyperfine (ih-)RIDME technique, which would be useful, for instance, in structural biology or dynamic nuclear polarisation experiments.

To test a structured electronic health record (EHR) case review process to identify diagnostic errors (DE) and diagnostic process failures (DPFs) in acute care.
We adapted validated tools (Safer Dx, Diagnostic Error Evaluation Research [DEER] Taxonomy) to assess the diagnostic process during the hospital encounter and categorized 13 postulated e-triggers. We created two test cohorts of all preventable cases (n=28) and an equal number of randomly sampled non-preventable cases (n=28) from 365 adult general medicine patients who expired and underwent our institution\'s mortality case review process. After excluding patients with a length of stay of more than one month, each case was reviewed by two blinded clinicians trained in our process and by an expert panel. Inter-rater reliability was assessed. We compared the frequency of DE contributing to death in both cohorts, as well as mean DPFs and e-triggers for DE positive and negative cases within each cohort.
Twenty-seven (96.4%) preventable and 24 (85.7%) non-preventable cases underwent our review process. Inter-rater reliability was moderate between individual reviewers (Cohen\'s kappa 0.41) and substantial with the expert panel (Cohen\'s kappa 0.74). The frequency of DE contributing to death was significantly higher for the preventable compared to the non-preventable cohort (56% vs. 17%, OR 6.25 [1.68, 23.27], p<0.01). Mean DPFs and e-triggers were significantly and non-significantly higher for DE positive compared to DE negative cases in each cohort, respectively.
We observed substantial agreement among final consensus and expert panel reviews using our structured EHR case review process. DEs contributing to death associated with DPFs were identified in institutionally designated preventable and non-preventable cases. While e-triggers may be useful for discriminating DE positive from DE negative cases, larger studies are required for validation. Our approach has potential to augment institutional mortality case review processes with respect to DE surveillance.

An EPR spectrometer has been developed that can be tuned to many frequencies in the range of ca 0.1-15 GHz. Applicability has been tested on ferrimyoglobin fluoride (MbF) and ferrimyoglobin cyanide (MbCN). MbF has a high-spin (S = 5/2) spectrum with 19F superhyperfine splitting that is only resolved in X-band along the heme normal. Low-frequency EPR also resolves the splitting in the heme plane. Measurement of linewidth as a function of frequency provides the basis for an analysis of inhomogeneous broadening in terms of g-strain, zero-field distribution, unresolved superhyperfine splittings and dipolar interaction. Rhombicity in the g tensor is found to be absent. MbCN (S = 1/2) has a highly anisotropic low spin (HALS) spectrum for which gx cannot be determined unequivocally in X-band. Low-frequency EPR allows for measurement of the complete spectrum and determination of the g-tensor.

A magnetophotoselection (MPS) investigation of the photoexcited triplet state of chlorophyll a both in a frozen organic solvent and in a protein environment, provided by the water-soluble chlorophyll protein (WSCP) of Lepidium virginicum, is reported. The MPS experiment combines the photoselection achieved by exciting with linearly polarized light with the magnetic selection of electron paramagnetic resonance (EPR) spectroscopy, allowing the determination of the relative orientation of the optical transition dipole moment and the zero-field splitting tensor axes in both environments. We demonstrate the robustness of the proposed methodology for a quantitative description of the excitonic interactions among pigments. The orientation of the optical transition dipole moments determined by the EPR analysis in WSCP, identified as an appropriate model system, are in excellent agreement with those calculated in the point-dipole approximation. In addition, MPS provides information on the electronic properties of the triplet state, localized on a single chlorophyll a pigment of the protein cluster, in terms of orientation of the zero-field splitting tensor axes in the molecular frame.

Membrane-active peptides are a promising class of antimicrobial and anticancer therapeutics. For this reason, their molecular mechanisms of action are currently actively investigated. By exploiting Electron Paramagnetic Resonance, we study the membrane interaction of two spin-labeled analogs of the antimicrobial and cytotoxic peptide trichogin GA IV (Tri), with opposite bioactivity: Tri(Api8), able to selectively kill cancer cells, and Tri(Leu4), which is completely nontoxic. In our attempt to determine the molecular basis of their different biological activity, we investigate peptide impact on the lateral organization of lipid membranes, peptide localization and oligomerization, in the zwitter-ionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) model membrane We show that, despite their divergent bioactivity, both peptide analogs (i) are membrane-bound, (ii) display a weak tendency to oligomerization, and (iii) do not induce significant lipid rearrangement. Conversely, literature data show that the parent peptide trichogin, which is cytotoxic without any selectivity, is strongly prone to dimerization and affects the reorganization of POPC membranes. Its dimers are involved in the rotation around the peptide helix, as observed at cryogenic temperatures in the millisecond timescale. Since this latter behavior is not observed for the inactive Tri(Leu4), we propose that for short-length peptides as trichogin oligomerization and molecular motions are crucial for bioactivity, and membrane binding alone is not enough to predict or explain it. We envisage that small changes in the peptide sequence that affect only their ability to oligomerize, or their molecular motions inside the membrane, can tune the peptide activity on membranes of different compositions.

Nucleoside triphosphates (NTPs) are used as chemical energy source in a variety of cell systems. Structural snapshots along the NTP hydrolysis reaction coordinate are typically obtained by adding stable, nonhydrolyzable adenosine triphosphate (ATP) -analogues to the proteins, with the goal to arrest a state that mimics as closely as possible a physiologically relevant state, e.g., the pre-hydrolytic, transition and post-hydrolytic states. We here present the lessons learned on two distinct ATPases on the best use and unexpected pitfalls observed for different analogues. The proteins investigated are the bacterial DnaB helicase from Helicobacter pylori and the multidrug ATP binding cassette (ABC) transporter BmrA from Bacillus subtilis, both belonging to the same division of P-loop fold NTPases. We review the magnetic-resonance strategies which can be of use to probe the binding of the ATP-mimics, and present carbon-13, phosphorus-31, and vanadium-51 solid-state nuclear magnetic resonance (NMR) spectra of the proteins or the bound molecules to unravel conformational and dynamic changes upon binding of the ATP-mimics. Electron paramagnetic resonance (EPR), and in particular W-band electron-electron double resonance (ELDOR)-detected NMR, is of complementary use to assess binding of vanadate. We discuss which analogues best mimic the different hydrolysis states for the DnaB helicase and the ABC transporter BmrA. These might be relevant also to structural and functional studies of other NTPases.

During the last years, the food industry is working on the replacement of high energy methodologies with more sustainable techniques for the encapsulation of natural preservatives, in order to enhance their effectiveness as food additives. In the present study, nisin, an antimicrobial agent, was encapsulated in essential oil-containing microemulsions. More specifically, rosemary, thyme, oregano, and dittany essential oil-containing microemulsions were formulated to encapsulate nisin enhancing the system\'s overall antimicrobial activity. The systems were investigated for the interfacial properties and size of the surfactants\' monolayer using electron paramagnetic resonance spectroscopy and dynamic light scattering. Subsequently, nisin-loaded microemulsions were tested for their antimicrobial activity against Lactococcus lactis, Staphylococcus aureus, Listeria monocytogenes, and Bacillus cereus, using the well diffusion assay. Finally, this technique was validated by a killing assay. Overall, this study provides important information on the antibacterial activity of nisin-loaded nano-carriers enhanced by essential oils, in relation to the microemulsions\' structure.

The oxidative stability of myrtle hydroalcoholic extracts was measured, over storage time, with the EPR spin trapping method under forced ageing conditions. The extracts were prepared with 150 and 300 g l-1 of berries and extraction media with ethanol ranging from 60 to 90%. Two radicals were detected: the PBN-1-hydroxyethyl adduct and the tert-butyl aminoxyl radical. A dimensionless parameter (Ω) calculated on the basis of the lag time, the rate of formation and concentration of the radical species was used to estimate the extracts\' oxidative stability. Ω was strongly influenced by the extraction medium, being lower in extracts with ethanol 60%, and by the time of storage. An inverse correlation was calculated between Ω and ellagic acid concentration, thus suggesting the role of this phenolic acid in the antioxidant properties of the extracts. The radical scavenging activity of the extracts against the hydroxyl radical was also measured.